Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes

Abstract

Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model. Three liposomal formulations (PEGylated or not) were prepared and validated to have a similar mean diameter, monodisperse distribution, and neutral zeta potential. The pharmacokinetic properties of each liposome were evaluated in healthy animals, while the biodistribution and scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle ratios were not statistically different between the PEGylated and non-PEGylated liposomes. While PEGylation is a well-established strategy for increasing the blood circulation of nanostructures, in our study, the use of polymer coating did not result in a better in vivo profile. Further studies must be carried out to confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor treatment.

Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells

“…As reference, MSNs functionalized with a PEG chain, CPT-PEG@MSN-DOX-OH, were prepared (Scheme 3a). As expected, the recorded zeta potential was close to neutrality, +4 mV [37]. The dependence of the zeta potential with the pH was monitored in a range of pHs from 8.0 to 5.0 ( Figure S8).…”

Immunological and Toxicological Considerations for the Design of Liposomes

“…More recently, there is increased research interest in formulations of lipid-drug (or photosensitizer) conjugates to improve the pharmacokinetics and therapeutic index of liposomal therapeutics [43][44][45][46][47]. Similarly, the incorporation of PEG, a polymeric steric stabilizer, is widely used to increase the blood circulation time of liposomal formulations [48,49]. The addition of PEG into liposomal doxorubicin extended the terminal half-life from 16.4 h to 77 h in patients with metastatic breast cancer [50,51].…”

Targeting lipid droplet lysophosphatidylcholine for cisplatin chemotherapy

“…Liposome has been applied in pharmaceutics for decades as a drug carrier 48,49 and is particularly effective for delivering poor water-soluble or highly toxic small-molecule compounds. 50 The addition of drug efficacy-enhancing lipids while manufacturing liposomes has been proposed in pharmaceutics. 51 However, there have…”